Brain imaging is used to study cerebral metabolic, electrophysiological and structural correlates of drug abuse. Efforts in technical development have yielded an improved form of a conventional model for calculation of cerebral metabolic rate(s) for glucose (CMRglc). The new model allows quantitative analysis of PET data without the need for arterial blood sampling and without the need for collecting blood samples during the early phase of the procedure. Positron emission tomography (PET) and electroencephalography (EEG) of human subjects show that euphoriants reduce global and regional CMRglc, and increase alpha power. The changes in CMRglc and EEG alpha power are correlated with self reports of feeling good, as measured by a subscale of the Addiction Research Center Inventory. Buprenorphine, a mixed opioid agonist, decreases regional CMRglc (rCMRglc) similar to effects produced by morphine and cocaine. Likewise, nicotine decreases RCMRGLC; however, the decreases are greater in smokers than in non-smokers, consistent with magnitudes of euphorigenic effects of nicotine in the two populations. As part of a clinical trial designed to test the effectiveness of peptide T on AIDS dementia, the correlation of the effect of peptide T on CMRglc with its effect on the progression of the disease is being tested. To determine whether differences in cerebral metabolism observed between drug abusers and matched controls represent a predisposition toward drug abuse or changes due to drug abuse, rates of cerebral metabolism and blood flow in twins discordant for drug abuse are being studied. Magnetic resonance imaging (MRI) is used to study brain structure, as related to neuropsychological performance in substance abusers. Correlations between planimetric MRI measurements and neuropsychological tests indicate that deficits in frontal areas of the brain may mediate the neuropsychological performance impairments in substance abusers. New studies will concentrate on relations of volumetric MRI measurements to performance and personality measures in substance abusers.